Kisspeptin-54 injection induces a physiological luteinizing hormone surge and ovulation in mice

Owen, C. M.; Zhou, Xiang; Bernard, Daniel; Jaffe, Laurinda A.

doi:10.1093/biolre/ioab067

“…LH release was stimulated by intraperitoneal injection of kisspeptin (Owen et al, 2021), a neuropeptide that causes gonadotropin releasing hormone to be secreted from the hypothalamus, which in turn causes release of LH into the bloodstream (Stevenson et al, 2022). The rise in serum LH peaks ~1.5 hours after kisspeptin injection and is comparable in amplitude and duration to the endogenous LH surge (Owen et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

“…However, LH-stimulated granulosa cell motility has not been investigated in intact ovarian follicles. By using mice with an HA epitope tag on the endogenous LH receptor such that its localization could be visualized [8], and by collecting ovaries for imaging at defined times after eliciting a physiological LH surge by injection of kisspeptin [36], we obtained a precise timecourse of changes in localization of mural granulosa cells expressing the LH receptor over the period leading to ovulation. We discovered that LH stimulates granulosa cells that express its receptor to extend inwards in the follicle, intercalating between other granulosa cells.…”

Section: Introductionmentioning

confidence: 99%

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle

Owen

¹

,

Jaffe

²

2023

Preprint

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Luteinizing hormone (LH) induces ovulation by initiating signaling by the mural granulosa cells that surround a mammalian oocyte in an ovarian follicle. However, much remains unknown about how LH activation of its receptor (LHR) modifies the structure of the follicle such that the oocyte is released and the follicle remnants are transformed into the corpus luteum. The present study shows that the preovulatory surge of LH stimulates LHR-expressing granulosa cells, initially located almost entirely in the outer layers of the mural granulosa, to rapidly extend inwards, intercalating between other cells. The proportion of LHR-expressing cell bodies in the inner half of the mural wall increases until the time of ovulation, with no change in the total number of cells expressing the receptor. Many of the initially flask-shaped cells appear to detach from the basal lamina, acquiring a rounder shape with multiple filipodia. Following the ingression of the LHR-expressing cells, but still hours before ovulation, the follicular wall develops numerous invaginations and constrictions. LH stimulation of granulosa cell ingression may contribute to changes in the follicular structure that enable ovulation.

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“…We recently reported that kisspeptin-54 induces surge-like LH release in juvenile mice. Although the duration of the LH increase is shorter than natural surges, these mice still ovulate efficiently ( Owen et al, 2021 ). Thus, both the amplitude and duration of natural LH surges are greater than actually needed to induce ovulation in mice.…”

Section: Discussionmentioning

confidence: 99%

Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

Toufaily

¹

,

Fortin

²

,

Alonso

³

et al. 2021

eLife

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Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.

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“…We recently reported that kisspeptin-54 induces surge-like LH release in juvenile mice. Although the duration of the LH increase is shorter than natural surges, these mice still ovulate efficiently (67). Thus, both the amplitude and duration of natural LH surges are greater than actually needed to induce ovulation in mice.…”

Section: Effects Of the Chicken C-tail On Gonadotropin Synthesis And Secretionmentioning

confidence: 95%

Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

Toufaily

¹

,

Fortin

²

,

Alonso

³

et al. 2021

Preprint

Self Cite

0

View full text Add to dashboard Cite

Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.

show abstract

Kisspeptin-54 injection induces a physiological luteinizing hormone surge and ovulation in mice

Abstract: Intraperitoneal injection of kisspeptin-54 induces a surge-like release of luteinizing hormone that stimulates ovulation in mice.

Cited by 8 publications

References 10 publications

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle

Luteinizing hormone stimulates ingression of mural granulosa cells within the mouse preovulatory follicle

Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

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